Bisoprolol which is a highly selective antagonist (β-blocker) of a β1-receptor of sympathetic nerve has been used for improving essential hypertension, angina pectoris and arrhythmia, and a fumarate thereof is orally administered as a tablet. On the other hand, in the case of oral administration, there are encountered problems that the sustention of the effects of bisoprolol is not sufficient; and that the concentration thereof in blood which is more than necessary is temporarily found after the administration, whereby side effects easily occur. In order to improve these problems, a percutaneous administration device has been desired.
In β-blockers, although various oral agents have been developed so far, reports on side effects such as irritation on a gastrointestinal mucosa have not been found in the oral administration. However, in view of the fact that the skin irritation which is characteristic to the drug occurs in the drug administration route through a skin, it was very difficult from the viewpoint of practical use to choose them as a drug for percutaneous absorption preparation. As to bisoprolol which is a β-blocker, there was also a possibility that when formed in a percutaneous absorption preparation, the skin irritation is revealed by the drug.
Although a bisoprolol-containing patch is described in, for example, Patent Documents 1 and 2, investigations have been made with focusing on stably keeping the concentration in blood, and it is hard to say that its skin irritation is thoroughly investigated.
Furthermore, as to such a bisoprolol-containing patch, repeated application is desired for the purpose of obtaining a sufficient therapeutic or preventive effect. In these patent documents, the repeated administration for repeating peeling and application every 24 hours is supposed. However, in such a patch, since a maximum value of human skin permeation rate exceeds 30 μg/cm2/hr, there is a high possibility that strong skin irritation by bisoprolol is generated depending upon a patient. As has been described, a percutaneous administration device in which the skin irritation during the application, especially at the time of peeling is thoroughly reduced and by which a therapeutically or preventively effective amount of bisoprolol can be persistently administered into a living body has not been known yet.    Patent Document 1: WO 2005/011662    Patent Document 2: WO 2006/080199